Since the start of the HIV epidemic, more than 60 million people have been infected with the virus. Currently, 42 million individuals are living with AIDS worldwide, and more than 20 million people have died as a consequence of the disease. Highly active anti-retroviral therapy (HAART), defined as a combination therapy of drugs capable of inhibiting HIV replication and lowering plasma viral load to undetectable level, is currently used as the standard care for HIV-infected patients. Despite the recent success in the development of this drug therapy, several limitations, such as the failure in eradicating the infection, toxic side effects, the emergence of drug-resistant viruses, together with its high cost, represent the challenges for achieving a long-term control of the progression of the HIV infection in infected individuals. Although there is no doubt that anti-retroviral drugs remain the reference treatment for HIV-1 infection, it is now generally accepted that we must broaden our treatment strategies focusing on the improvement of safety and efficacy of therapies and the simplification of disease management. It has been demonstrated that short interruptions of drug treatment can act as a boost for HIV immunity, and this has raised the question whether immune-based therapies could be considered as useful and powerful tools for enhancing immune responses to HIV, thereby limiting the use of anti-retroviral drugs and improving the efficacy of the treatment in a long-term strategy? An increasing interest in immune-based therapies for HIV infections stems from emerging data suggesting that some immune correlates can play a key role in reducing virus replication. In particular, it has been shown in animal models as well as in humans that both T helper (Th) cells and cytotoxic T lymphocytes (CTLs) are important in containing HIV replication (Jin et al., 1999; Rosenberg et al., 1997; Schmitz et al., 1999). Therefore, enhancing immune control of the virus in terms of the strength and extent of HIV-specific cellular responses might have a clinical benefit or enhance the efficacy when we use antiviral drugs. Several strategies of immunotherapy have been assessed in HIVinfected patients. They include the use of cytokines, immune cells, drugs inhibiting T-cell activation, and vaccines. Therapeutic immunization may be intended as a complementary approach to anti-retroviral drug therapy to induce an effective control of HIV replication, thus preventing immunologic defects caused by virus spreading and, at the same time, permitting long periods of an absence of therapy. Currently, the development of HIV-1 vaccines is focusing on strategies capable of eliciting effective T-cell responses. An ensemble of studies has now revealed that dendritic cells (DCs) play a crucial role in linking innate and adaptive immunity against pathogens. Several factors are important in designing an effective therapeutic vaccine, but the capability of the antigen formulation targeting DCs in sufficient amounts to trigger an effective response represents one of the most significant prerequisites. The complex biology of DCs, the heterogenicity of these cells and of their functions in the regulation of the immune response, and the importance of recent progress of knowledge in the field of vaccine research have been extensively described in other chapters of this book. This chapter will focus on the state of the art of immunotherapy for the treatment of HIV-1 infection, with particular emphasis on DCs as targets and tools of HIV vaccines.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)